OBJECTIVES: To examine the effect of removal or reduction in prescription copayments, in the absence of disease management plans, on adherence to prescription medications. METHODS: Six electronic databases were systematically searched for relevant articles, along with hand searches of references in review articles and the included studies. Studies were included if they involved an intervention which reduced or removed copayments and if the outcome was objectively measured adherence. Study designs permitted were randomised controlled trials, time series analyses, controlled before/after studies and cohort studies. Studies were excluded if the intervention was part of a disease management plan. Study exclusion, data extraction and quality appraisal were carried out by two independent reviewers. Data were qualitatively synthesised. RESULTS: Nine out of 40 studies were included. One study was an RCT; the remainder were all controlled before/after studies. There were 144,991 cases and 125,057 controls in this review. The mean age was 54.39yrs and 55.21yrs for the cases and controls respectively. 44.79% of the cases were female, whereas 49.54% of the controls were female. Four studies analysed the effect of reduced copayment, 4 studies analysed the effect of a removed copayment and 1 study analysed both. Only one study received a strong quality assessment, one study was rated as moderate, and the remainder were rated as weak. Seven studies showed a significant improvement in adherence. Two studies did not show an improvement in adherence. CONCLUSIONS: This review concludes that there is some evidence of small increases in adherence on the removal or reduction of copayments. However, confounders and biases between the included studies were variable. Future studies should concentrate on establishing associations between reduced cost-sharing and clinical and economic outcomes.